perioperative treatment in resectable gastric cancer with spartalizumab (pdr001) in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (flot)

Conditions: Gastric Cancer by AJCC V8 Stage; Resectable Carcinoma

Summary: multicenter, open-label, non randomized, phase 2 trial in resectable gastric or gastroesophageal junction adenocarcinoma: perioperative treatment by spartalizumab (pdr001) in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (flot)


Eligibility criteria:
inclusion criteria: * age ≥ 18 years * untreated localized gastric or gej adenocarcinoma considered resectable (clinical stage ≥ct2 and/or cn+ and no metastasis) * histologically confirmed adenocarcinoma * ecog performance status score of 0 or 1 * tumor tissue must be provided for biomarker analyses (fresh or archival with an ffpe tissue block) * all subjects must consent to allow the acquisition of blood samples for performance of correlative studies * screening laboratory values must meet the following criteria: * wbc ≥ 2000/ mm³ * neutrophils ≥ 1500/ mm³ * platelets ≥ 100 000/ mm³ * hemoglobin ≥ 9.0 g/dl * bilirubin ≤ 1.5 x uln, ast and alt ≤ 3 x uln * measured or calculated creatinine ≥ 50 ml/min clearance (crcl) (using the cockcroft-gault formula) * potassium ≥ lln * magnesium ≥ lln * calcium ≥ lln * female subject of childbearing potential must have a negative urine or serum pregnancy test within 72h before study start * subject in reproductive age must be willing to use adequate contraception during the study and at least 9 months in men and 12 months in women after the last dose of investigational drug. in addition, given the toxicities observed on the male reproductive system, a conservation of gametes will be proposed for men, as usually in routine practice * subject affiliated to a social security regimen * patient has signed informed consents obtained before any trial related activities and according to local guidelines exclusion criteria: subject with any distant metastasis * subject with no recovering from the effects of major surgery or significant traumatic injury within 14 days before inclusion * documented significant cardiovascular disease within the past 6 months before the first dose of study treatment, including: history of congestive heart failure (defined as nyha iii or iv), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis * history of anterior organ transplant, including stem cell allograft * pneumonitis or interstitial lung disease * history of other malignancy within the previous 3 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma) * subject with active, known, or suspected autoimmune disease * subject with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment gaspar protocol - eudract number: 2020-004497-21 - version 1.3 / 2021-01-18 page 8 sur 44 * known history of hiv or hbv infection * known active hcv infection * known history of active tuberculosis * vaccination with live vaccine within 30 days before the first dose of study treatment * prior treatment with an anti-pd-1, anti-pd-l1, anti-pd-l2 or any other antibody or drug specifically targeting t-cell co-stimulation or checkpoint pathways * recent or concomitant treatment with brivudine (herpes virostatic) * prior anticancer therapy for the current malignancy * known hypersensitivity to any of the study drugs or their excipients * chronic inflammable gastro-intestinal disease * uracilemia ≥ 16 ng/ml * qt/qtc \> 450 msec for men and \> 470 msec for women * peripheral neuropathy ≥ grade ii * uncontrolled diabetes * active infection requiring systemic therapy * participation in another therapeutic clinical study * patient deprived of liberty or placed under the authority of a tutor * patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Keywords: perioperative spartalizumab pdr001 gastric cancer